Chemistry of Anti-Doping: Deterring of Performance-Enhancing … · 2017. 7. 20. · This ACS Webinar was co-produced with the Partnership for Clean Competition “ Chemistry of Anti-Doping:

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www.acs.org/acswebinars Slides available now! Recordings are an exclusive ACS member benefit.

This ACS Webinar was co-produced with the Partnership for Clean Competition

“Chemistry of Anti-Doping: Deterring of Performance-Enhancing Drug Use by Athletes”

Larry Bowers President, LDBowers and former

CSO, US Anti-Doping Agency

Jason Schaff

Forensic Chemist,

US Government

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Chemistry of Anti-Doping:

Deterring Performance-Enhancing Drug

Use by Athletes

Larry D. Bowers, PhD

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It works!

There are powerful incentives to dope Lack of trust that others will not dope and thereby

defraud the individual of their legitimate rewards

Concern that anti-doping programs do not catch cheaters

Concern that the sport organization is not committed to eliminating doping

Concern that some countries are not committed to eliminating doping

Huge personal and financial rewards

Immediate gratification versus delayed sanction (time discounting)

“Win at all costs” mentality

Why do athletes dope?

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Doping is a rational choice

Decision regarding doping behavior is made by

evaluating the rewards versus risks

Doping is

Instrumental

Communal

Requires expertise

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Compliance and Sanction Threats

Deterrence is based on threat assessment

Certainty of being detected and

sanctioned

Severity of sanction

Timeliness (Celerity) of sanction

Perceptions are more important in

decision making than facts

Perceptual calibration

Perceptual deterrence

Perceptual (experiential) re-calibration

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Is Random Drug Testing a Threat?

Assume that an individual uses

a drug three times a month.

The detection window for the

drug is two days.

Assume that the drug testing

program tests 5% of the eligible

pool of athletes at random

each month.

How long does it take to detect

this drug user?

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• 4 months

• 9 months

• 4 years, 9 months



How long does it take to detect this drug user?

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Audience Challenge Question ANSWER THE QUESTION ON BLUE SCREEN IN ONE MOMENT

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Does testing change behavior?

Zorzoli M, Rossi F. Drug Test Anal 2010; 2: 542-7.

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How can we influence perceptions?

Perceptual re-calibration – ensure that experience with the system

reinforces the certainty of being caught

Research to improve detection of doping agents

Research to identify new doping agents

Collection of information to guide testing strategies

“Non-analytical” cases

Ambiguity aversion – uncertain situations increase certainty of

detection

No-advance-notice out-of-competition sample collection

Alternative matrices (e.g., dried plasma spots) to cost-effectively increase testing numbers

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Synthetic anabolic steroid

detection

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Steroid Metabolism (Phase I)

Reduction of double bond

Reduction or oxidation of hydroxyl/keto group

Reduction or oxidation of hydroxyl/keto group

Aromatization to form estrogens

6β hydroxylation

16α/β-hydroxylation

Testosterone Androsterone

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Steroid Metabolism (Phase II)

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• Several days

• Several weeks

• Several months

• Several years

Synthetic anabolic steroids can be detected in urine for how long after administration?

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Detection of Urinary Steroids

GC - MS and GC - MS/MS

SPE sample clean-up

-glucuronidase cleavage

Extract free steroids with t-butyl-

methyl ether or pentane

Derivatization with MSTFA/

NH4I/C2H4SH

GC - MS SIM analysis

HPLC - MS/MS

SPE sample clean-up

Optional conjugate cleavage

Extract free steroids

LC – MS/MS analysis

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Pros & Cons of Derivatization

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Methandienone (Dianabol) Epi-methandienone

~ 2-3 days

Edlund PO, Bowers LD, Henion, JD. J Chromatogr 1989; 487: 341-56.

??

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Schänzer W et al. Rapid Commun Mass Spectrom 2006; 20: 2252-8.

~ 6 days ~ 19 days

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Long-lived Steroid Metabolites

Tetrahydrogestrinone (THG) Tetrahydro-epi-methyltestosterone-3-sulfate

17-epi-stanozolol-N-glucuronide

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Detection Window for

Stanozolol Glucuronide Conjugates

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Challenges with long-lived

metabolite analysis

Decreasing limits of detection and identification of long-

lived metabolites allows detection of anabolic steroids for

many months

Re-analysis of samples from past Olympic Games results

in more positive urine samples and medal re-distribution

Detection of pg/mL metabolites in urine raises

interpretive challenges

Residual metabolites versus new use

Inadvertent ingestion of contaminated meat or grain

“Off-label” medical treatment (e.g., clomiphene for male

infertility)

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Peptide and protein doping

agent detection

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• True

• False

Peptide hormones (less than 75 L-amino acids) can be detected in urine.

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Insulin-like Growth Factor 1

C C

C C

S

R F

G A

E L

V D

D L R

R

L

M

L Q F V C

C Y

E

A

G

P

E

I

L

E

D

V I G T Q P A R R

S S S

A S

K

A

P

K

L

P A

G

T

P

K

N

F Y

F G

R D

Y

G

G

Molecular mass: 7649 Daltons

Blood concentration: 30-400 ng/ml

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LC-MS/MS Quantification of IGF-1

Interlaboratory (n=5) study of IGF-1 bottom-up method

Working group has developed serum reference

material with a consensus concentration assigned for LC-MS/MS work

Collaborating with the National Institute for Science and Technology (NIST) to develop an ISO traceable serum-based reference material

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Urinary Analysis of GHRP2

(D-Ala)-(D-β-Nal)-Ala-Trp-(D-Phe)-Lys –NH2

GHRP 2

(D-Ala)-(D-β-Nal)-Ala-NH2

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Summary and Conclusions

Doping/cheating in sport is a reflection of society and its problems as a whole

Anti-doping policies should be designed to deter the use of performance-enhancing drugs and involve complex interdisciplinary effort

Perceptual deterrence model provides guidance for optimizing programs to achieve behavior change

Research is an important factor in increasing the perceived certainty of detection, which is the primary factor in assessing risk

Anti-doping testing requires a skilled laboratory staff with expertise in analytical science, biochemistry, clinical chemistry, exercise physiology, pharmacology, hematology, and endocrinology

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Jason Schaff

Forensic Chemist,

US Government

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www.cleancompetition.org


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Jason Schaff

Forensic Chemist,

US Government

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“Lauren was an excellent, professional, dynamic, energetic, and inspiring presenter. Because of this ACS Webinar, I am anxious and motivated to make some time to delve into improving my LinkedIn profile and content!”

Meg Draeger STEMM Coordinator Chaminade Julienne Catholic High School

Be a featured fan on an upcoming webinar! Write to us @ [email protected]

How has ACS Webinars benefited you?

®

7/18/2017

22

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youtube.com/acswebinars


44

Benefits of ACS Membership


Chemical & Engineering News (C&EN) The preeminent weekly news source.

NEW! Free Access to ACS Presentations on Demand® ACS Member only access to over 1,000 presentation recordings from recent ACS meetings and select events.

NEW! ACS Career Navigator Your source for leadership development, professional education, career services, and much more.

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Chemistry of Anti-Doping: Deterring of Performance-Enhancing … · 2017. 7. 20. · This ACS Webinar was co-produced with the Partnership for Clean Competition “ Chemistry of Anti-Doping: